Optimal CD4 Count for Initiating HIV Treatment

BACKGROUND: In HIV infection, dynamic marginal structural models have estimated the optimal CD4 for treatment initiation to minimize AIDS/death. The impact of CD4 observation frequency and grace periods (permitted delay to initiation) on the optimal regimen has not been investigated nor has the performance of dynamic marginal structural models in moderately sized data sets-two issues that are relevant to many applications. METHODS: To determine optimal regimens, we simulated 31,000,000 HIV-infected persons randomized at CD4 500-550 cells/mm to regimens "initiate treatment within a grace period following observed CD4 first 0.5% lower AIDS-free survival compared with the true optimal regimen. CONCLUSIONS: The optimal regimen is strongly influenced by CD4 frequency and less by grace period length. Dynamic marginal structural models lack precision at moderate sample sizes.